RECK Negatively Regulates Matrix Metalloproteinase-9 Transcription

¹Antibiotics Laboratory and Chemical Biology Department, Advanced Science Institute, RIKEN and ²Graduate School of Science and Engineering, Saitama University, Saitama, Japan

^* To whom correspondence should be addressed. E-mail: simizu{at}riken.jp.

	Abstract

RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of some matrix metalloproteinases (MMP), thereby suppressing tumor cell metastasis; however, the detailed mechanism is still obscure. In this study, we compared the gene expression profiles between mock- and RECK-transfected HT1080 cells and showed that RECK decreases MMP-9 mRNA levels but not other MMP mRNA levels. Moreover, treatment with RECK-specific siRNA increased MMP-9 mRNA in RECK-expressing cells. The promoter assay showed that MMP-9 promoter activity was suppressed by RECK and that RECK-mediated suppression of MMP-9 promoter activity requires 12-O-tetradecanoylphorbol-13-acetate–responsive element (TRE) and B sites. Moreover, the binding ability of Fra-1 and c-Jun to TRE within the MMP-9 promoter region was suppressed by RECK. Thus, these results show that RECK is a negative regulator of MMP-9 transcription. [Cancer Res 2009;69(4):1502–8]

Key Words: RECK, invasion, matrix metalloproteinase-9, glycosylphosphatidylinositol-anchored protein, Fra-1